Bis(dibutyldithiocarbamato-S,S')copper

Endpoint summary

Description of key information

A study was available for the acute oral toxicity in rats on CDBC: the oral LD50 is higher than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-18 april 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

a minor deviation (relative humidity recorded in the animal room was sometimes outside of range specified in the protocol), not considered to have compromised the validity or integrity od the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories (69210 L'Arbresle, France)
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 166 ± 5 g (males) and 142 ± 12 g (females)
- Fasting period before study: yes, an overnight period af approximately 18 hours before dosing (but free access to water)
- Housing: in polycarbonate cages
- Diet (e.g. ad libitum): free access to A04C pelleted diet (UAR, Villemoisson Epinay sur orge, France)
- Water (e.g. ad libitum): filtered water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°c
- Humidity (%):30 to 70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

other: methylcellulose

Details on oral exposure:

The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 5 ml glass syringe (0.05 ml graduations).
The volume adminitered to each animal was adjusted according to body weight determined on the day of treatment (Volume administered: 10 ml/kg).

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males + 5 females per group

Control animals:

no

Details on study design:

- Clinical signs: examined frequently during the hours following administration of the test substance and then at least once a day until the end of experiment
- Mortality: recorded at least twice a day
- Body weight: measured just before administration then on days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with similar initial body weight.
- Necropsy:
. macroscopic examination of the main organs: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities.
. microscopic examination: no

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: only one female died

Mortality:

1 female died on day 1, with 30 minutes following treatment. No clinical signs were observed prior to death.

Clinical signs:

other: No clinical signs occurred in treated animal.

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Table 1: Individual and mean body weight and weekly body weight change (g)

Dose (mg/kg)	Volume (mL/kg)	Sex	Animals	Days
				1	(1)	8	(1)	15
2000	10	male	01	168	72	240	54	294
			02	167	72	239	57	296
			03	157	81	238	60	298
			04	167	79	246	58	304
			05	171	95	266	71	337
			M	166	80	246	60	306
			SD	5	9	12	7	18
2000	10	female	06	134	33	167	31	198
			07	144	41	185	29	214
			08	140	-	-	-	-
			09	160	52	212	47	259
			10	130	35	165	19	184
			M	142	40	182	32	214
			SD	12	9	22	12	33

(1): body weight gain

M= mean; SD = standard deviation

-: animal found dead during the study

 

Table 2: Mean body weight of control rats (g)

Dose (mg/kg)	Volume (mL/kg)	Sex	days
				1	8	15
0	10	male	M	178	253	300
			SD	12	19	24
			n	35	35	35
0	10	female	M	141	184	208
			SD	10	14	18
			n	35	35	35

M= mean; SD = standard deviation; n = number of animals

 

Table 3: Mean body weight change of control rats (g)

Dose (mg/kg)	Volume (mL/kg)	Sex	days
				1 to 8	8 to 15
0	10	male	M	75	47
			SD	12	11
			n	35	35
0	10	female	M	43	23
			SD	10	6
			n	35	35

M= mean; SD = standard deviation; n = number of animals

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under these experimental conditions, the oral LD50 of CDBC is higher than 2000 mg/kg bw in rat.

Executive summary:

The acute oral toxicity of the test substance CDBC was evaluated in rats according to OECD (401) and EC guidelines, and in compliance of GLP. The test substance was administered by oral route (gavage) to one group of ten fasted rats (5 males and 5 females). The test substance was prepared in 0.5 % methylcellulose and was administered to the animals at the dose of 2000 mg/kg, under a volume of 10 ml/kg. Clinical signs, mortality and bodyweight gain were checked for a period of up to 14 days following the single administration of the test substance. All animals were subjected to necropsy.

one female died on day 1, within 30 minutes following treatment. No clinical signs were observed prior to death. No clinical signs and no deaths occurred in the other treatment animals. The body weight gain of the surviving animals was similar to that of historical control animals. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the oral LD50 of CDBC is higher than 2000 mg/kg bw in rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

It is a reliable study with a klimisch score of 1 (OECD guideline).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity (Manciaux 2001):

The acute oral toxicity of the test substance CDBC was evaluated in rats according to OECD (401) and EC guidelines, and in compliance of GLP. The test substance was administered by oral route (gavage) to one group of ten fasted rats (5 males and 5 females). The test substance was prepared in 0.5 % methylcellulose and was administered to the animals at the dose of 2000 mg/kg, under a volume of 10 ml/kg.

One female died on day 1, within 30 minutes following treatment. No clinical signs were observed prior to death. No clinical signs and no deaths occurred in the other treatment animals. The body weight gain of the surviving animals was similar to that of historical control animals. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the oral LD50 of CDBC is higher than 2000 mg/kg bw in rat.

Justification for classification or non-classification

Proposed self-classification according to the Regulation (EC) No 1272/2008: Not classified